Abstract
G-rich nucleic acids can form non-canonical G-quadruplex structures (G4s) in which four guanines fold in a planar arrangement through Hoogsteen hydrogen bonds. Although many biochemical and structural studies have focused on DNA sequences containing successive, adjacent guanines that spontaneously fold into G4s, evidence for their in vivo relevance has recently begun to accumulate. Complete sequencing of the human genome highlighted the presence of ∼300 000 sequences that can potentially form G4s. Likewise, the presence of putative G4-sequences has been reported in various viruses genomes [e.g., Human immunodeficiency virus (HIV-1), Epstein–Barr virus (EBV), papillomavirus (HPV)]. Many studies have focused on telomeric G4s and how their dynamics are regulated to enable telomere synthesis. Moreover, a role for G4s has been proposed in cellular and viral replication, recombination and gene expression control. In parallel, DNA aptamers that form G4s have been described as inhibitors and diagnostic tools to detect viruses [e.g., hepatitis A virus (HAV), EBV, cauliflower mosaic virus (CaMV), severe acute respiratory syndrome virus (SARS), simian virus 40 (SV40)]. Here, special emphasis will be given to the possible role of these structures in a virus life cycle as well as the use of G4-forming oligonucleotides as potential antiviral agents and innovative tools.
Highlights
G-rich nucleic acids can form non-canonical Gquadruplex structures (G4s) in which four guanines fold in a planar arrangement through Hoogsteen hydrogen bonds
X-ray diffraction data clearly showed that the guanosine moieties in these gels were arranged in a tetrameric organization linked by eight Hoogsteen hydrogen bonds (Figure 1) [2,3]
Short RNA templates from the central region of the HIV1 genome contain G-rich sequences near the central polypurine tract at the 3 end of the pol gene (IN coding sequence); this is a region where one of the two primers used for synthesizing the (−) strand DNA is produced during reverse transcription
Summary
Without clear signaling and tight regulation, extremities present in linear chromosomes could be recognized as damage DNA and it would be deleterious for the cell if processed as such by repair mechanisms [45]. Telomeres are nucleoprotein structures found at the end of chromosomes protecting the genome from instability. DNA2, a helicase/nuclease that cleaves G4s, is involved in maintaining telomere integrity [53,54] These observations clearly establish that telomeric G4s are crucial structures for regulating telomere maintenance, providing a mechanism for controlling cell proliferation [55,56]. At the 3 ends of telomeres, if the G-rich overhang is longer than four TTAGGG repeats (>23 nucleotides), it can fold over itself and form secondary structures, including G4s (Figure 2a). The exact mechanism is more complicated as telomestatin derivatives present telomerase independent activity, most likely through targeting G4s involved in tumor growth elsewhere in the genome [62,63,64]
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